The safety and utility of low-intensity pulsed ultrasound for effective blood–brain barrier penetration in the treatment of glioblastoma: a scoping review protocol

Abstract Glioblastoma (GBM) is one of the most aggressive central nervous system tumours with suboptimal treatment options and associated poor prognosis. A major impediment to systemic treatment is the limitation of drug delivery to the tumour by the blood-brain barrier (BBB). Several novel techniques to permeate the BBB have been described, however of significant promise is the disruption of the blood brain barrier with low-intensity pulsed ultrasound (LIPU) to facilitate the delivery of varying therapeutic agents. This emerging technique has been demonstrated in clinical studies to enhance delivery of chemotherapeutic agents to the tumour. This study protocol seeks to guide the comprehensive review of literature concerning the safety and utility of LIPU for effective BBB penetration in the treatment of GBM. This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA ScR) guideline 2020. The search strategy was performed on four databases: PubMed, EMBASE, SCOPUS, and Cochrane Central Register of Controlled Trials. All observational and human randomised controlled studies describing the use of LIPU in the treatment of GBM will be included. Excluded studies include non-human randomized control trials, abstract only articles, letters to the editor, conference proceedings. Our outcomes include frequency of LIPU used, duration of intervention, clinical outcomes, complications, and challenges associated with the use of LIPU. This study aims to assess the safety and feasibility of this technique in the management of the GBM and proscribe its use if found effective to improve the outcomes in these patients.